A pilot study was conducted that demonstrated the ability of free access to a high-fat diet plus liquid Ensure (14% protein, 22% fat, and 64% carbohydrate) to induce severe obesity in male C57BL/6 mice. After 4 weeks, mice fed high fat plus Ensure (N = 6) had a 45% greater body weight and 470% greater fat mass than the control group fed a standard chow diet (24% protein, 12% fat, 64% carbohydrate) (N = 6). Mice fed with a high fat diet alone (14% protein, 59% fat, and 27% carbohydrate) (N = 6) increased body weight and fat mass by 35% and 370%, respectively, versus the chow-fed controls. The animals on the obesigenic diets ate the most calories, but after 4 weeks when the diets were switched to chow there was a dramatic decrease in food intake causing body weight and fat mass to approach control values after 4 additional weeks. These results suggested that diet-induced obesity is not permanent and may be reversed once the obesigenic environment is removed. [unreadable] [unreadable] We are presently conducting a full experiment using a longer period of obesity induction before switching the diets to standard chow. Furthermore, we are assessing changes of energy expenditure, adipocyte size distributions in various fat depots, inflammatory markers, various endocrine signals, insulin sensitivity, glucose and glycerol turnover, as well as organ mass changes during the induction and reversal of obesity. Various tissues are being collected for subsequent analysis of gene expression and protein changes.